1. Field of the Invention
The present invention relates to a Z-stilbenes derivative and a pharmaceutical composition thereof, more particularly, to a Z-stilbenes derivative which can inhibit microtubules polymerization and a pharmaceutical composition thereof.
2. Description of Related Art
The microtubule system of eukaryotic cells is an important target for the development of anticancer agents. For a more concrete description, the microtubule polymerization/depolymerization is a popular target for the development of new chemotherapy agents. A number of clinically used agents (such as paclitaxel, epothilone A, vinblastine, combretastatin A-4 (CA-4), dolastatin 10, and colchicines), taking microtubule polymerization/depolymerization as the target, all exhibit their anticancer properties by disrupting cellular microtubule structure and function resulting in mitotic arrest, as well as inhibiting the growth of epithelium of newly formed vasculature to shut down the blood supply to tumors (please refer to Jordan et. al., (1998) Med. Res. Rev. 18: 259-296).
Therefore, according to the microtubule system (such as tubulin polymerization/depolymerization) as the target for developing compounds, the new therapy used for the treatment or the prevention of cancers or cancer related symptoms, or the treatment of angiogenesis related disease, such as cardiovascular disease (e.g. atherosclerosis), chronic inflammation (e.g. rheumatoid arthritis or Crohn's disease), diabetes (e.g. diabetic retinopathy), psoriasis, and retinal neovascularization or corneal neovascularization can be developed (please refer to Griggs rt. al., (2002) Am. J. Pathol. 160(3): 1097-1103).
It is discovered that colchicine and combretastatin A-4, such as the following ZD6126, CA4P, and AVE-8062, can exhibit the anticancer property by rapidly depolymerizing microtubules of newly formed vasculature to shut down the blood supply to tumors:
The aforementioned compounds are now undergoing human clinical trials for either single use or combination use with chemotherapy drugs to inhibit cancers.
The analysis of Structure-Activity Relationship (SAR) can interpret the effect of the chemical structure on the activity so as to develop the most effective drugs to treat diseases. Through the analysis of SAR, it is found that the B ring of the aforementioned CA4P structure is the site on which the polar functional group(s) is often located. Thereby, new Z-stilbenes derivatives having anticancer activity can be developed by modifying the functional group(s) located on the B ring. In addition, the solubility of the CA-4 like compounds can be enhanced by introducing a phosphate group, amino group, or others. Therefore, considerable research focuses on developing novel Z-stilbenes derivatives different from conventional ones, having solubility, and exhibiting anticancer activity to afford a series of compounds, which can inhibit cancers.